We examined the effects of intravenous bolus injection of human neuropeptide Y (NPY, 100 micrograms) on the plasma growth hormone (GH) and prolactin (PRL) responses in 15 patients with prolactinoma (PRLoma). The GH and PRL responses to NPY were considered positive (a paradoxical increase) when an increase over baseline of at least 100% occurred. Although NPY did not affect PRL secretion in any of the patients examined, 60% (9 of 15) of the patients showed a significant rise in GH secretion after NPY. The presence or absence of the positive paradoxical increase in GH after NPY was not related to the age of the patients, basal PRL levels, the size of the pituitary adenoma (macro- or microadenoma), or the presence or absence of suprasellar extension of the adenoma. Although the underlying mechanism of the NPY stimulation of GH secretion and also its pathophysiological significance in PRLoma are open to question, the present observation may represent another example of paradoxical hormone responses which are occasionally found in functioning pituitary adenomas.